1. Field of the Invention
The present invention relates to a method of sterilizing a blood dialyzer having semipermeable membranes by .gamma.-ray irradiation. More particularly, the present invention relates to a method of sterilizing a blood dialyzer having semipermeable polymeric membranes by irradiating the dialyzer with .gamma.-rays, without deterioration of the polymeric membranes, while preventing an increase in the ultraviolet ray-absorbing property of the polymeric membranes due to the .gamma.-ray irradiation.
2. Description of the Related Art
As a typical method of sterilizing medical devices, for example, blood dialyzer having semipermeable polymeric membranes, an ethylene oxide gas sterilizing method, a high pressure steam sterilizing method and a .gamma.-ray sterilizing method are known. These sterilizing methods have both merits and demerits. In recent years, the high pressure steam sterilizing method and the .gamma.-ray sterilizing method have been commonly utilized due the merits of less residual toxicity and extreme ease of operation.
Nevertheless, the utilization of the high pressure steam sterilizing method is restricted to semipermeable membranes having a high heat resistance. Also, it is known that the .gamma.-ray sterilizing method is not appropriate for membrane materials comprising cellulose, cellulose esters or polymethyl methacrylate which have poor resistance to .gamma.-rays. Therefore, it was believed that the .gamma.-ray sterilizing method was difficult to be practically utilized to sterilize the blood dialyzer having semipermeable membranes made from the above-mentioned polymeric materials.
A specific method of sterilizing a blood dialyzer having semipermeable membranes made from a polymer having a low .gamma.-ray resistance by .gamma.-ray irradiation is disclosed in Japanese Unexamined Patent Publication (Kokai) No. 59-192,373. In this specific method, the .gamma.-ray irradiation is carried out in an inert gas atmosphere comprising carbon dioxide or nitrogen gas. This Japanese publication discloses that when the .gamma.-ray irradiation is applied to the membranes in an .gamma.-ray active (absorbent) gas atmosphere, for example, an oxygen gas atmosphere, the membranes are oxidized and thus deteriorate. This Japanese publication further states that by the specific method thereof, the membranes can be sterilized by the .gamma.-ray irradiation in a dry condition, while preventing the deterioration of the membranes.
This method is, however, disadvantageous in that since the resultant sterilized blood dialyzer is in a dry condition, the semipermeable membranes must be wetted and bubbles formed in the blood dialyzer must be completely removed before the blood dialyzer is subjected to practical use, and these operations require much labor and time and thus the omission of these operations is strongly demanded by medical institutions.
Also, Japanese Unexamined Patent Publication (Kokai) No. 52-99,679 discloses a method by which blood dialyzing membranes can be sterilized in a wetted condition by .gamma.-ray irradiation. In accordance with this method, the .gamma.-ray sterilizing method can be applied to the blood dialyzing membranes comprising cellulose or polymethyl methacrylate in a water-wetted condition.
The inventors of the present invention have investigated this method and found that when the .gamma.-ray sterilization is applied to a semipermeable polymeric membrane wetted only with water in a saturation amount or more, it is difficult to fully sterilize the polymeric membranes without substantial deterioration thereof. Especially, it has been confirmed that when this method is applied to semipermeable cellulose ester membranes, the above-mentioned difficulty significantly increases.
Further, Japanese Unexamined Patent Publication (Kokai) No. 5-192,397 discloses that when a blood dialyzer having semipermeable polymeric dialyzing membranes is sterilized by a .gamma.-ray irradiation, the derioration of the polymeric dialyzing membranes can be prevented by packing the blood dialyzer with an aqueous solution of 0.1 to 5.0% by weight of glycerol. This method is advantageous in that the deterioration of the dialyzing membranes can be avoided. However, this method is disadvantageous in that the .gamma.-ray irradiation causes the .gamma.-ray-irradiated aqueous glycerol solution packed in the blood dialyzer to contain a .gamma.-ray reaction product which exhibits an undesirable ultraviolet ray-absorbing property, and sometimes, an extract dissolved out from the sterilized polymeric membranes into the aqueous glycerol solution exhibits an ultraviolet ray-absorption value exceeding 0.1 which is an upper limit of safety margin of the extract.
Also, the aqueous glycerol solution allows bacteria to proliferate before the .gamma.-ray sterilization. Therefore, after the .gamma.-ray irradiation, the sterilized aqueous glycerol solution includes an increased amount of dead bacteria.
Accordingly, there has been a strong demand for a new .gamma.-ray sterilizing method for a blood dialyzer having semipermeable polymeric dialyzing membranes which can prevent or restrict the generation of an .gamma.-ray reaction product having an ultraviolet ray-absorption value exceeding the margin of safety of the blood dialyzer.